Catheter related septicemia is a serious problem potentially affecting an estimated 160 million catheter starts yearly in the U.S. alone. Evidence to date suggests that organisms invade at the catheter site to initiate a local infection. Topical antimicrobials including "Neosporin.RTM. Ointment" commercially available from Burroughs Welcome Co., Research Triangle Park, N.C., and iodophor ointments are widely used in an attempt to provide some protection from microbial invasion. Clinical studies attempting to determine the efficacy of these topical ointments has shown them to be of modest or no benefit in reducing rates of infection (Zinner, S. H., B. C. Denny-Brown, P. Braun, J. P. Burke, P. Toala and E. H. Kass. 1969. "Risk of Infection with Intravenous Indwelling Catheters: Effect of Application of Antibiotic Ointment." The Journal of Infectious Diseases. 120: 616-619; Morden, Carl W. 1969. "Application of Antibiotic Ointment to the Site of Venous Catheterization-A Controlled Trial". The Journal of Infectious Diseases. 120: 611-615; Maki, Dennis G. and Jeffrey D. Band. 1981. "A Comparative Study of Polyantibiotic and Iodophor Ointments in Prevention of Vascular Catheter-Related Infection". The American Journal of Medicine. 70: 739-744). Suggested reasons for the marginal benefits of these ointments have been proposed in the literature. The leading suspect is that since these ointments are petroleum jelly based, they are occlusive and not moisture vapor transmissive. Moisture from the body builds up under the ointment creating a beneficial environment for the bacteria and a pathway to the catheter. Additionally, ointments are greasy and poorly compatible with the transparent dressings or gauze and tape normally used to dress catheters. The ointment will either become absorbed by the gauze or dressing material, thereby not remaining at the site, or the ointments will undermine the adhesion of the transparent dressing and migrate under the dressing, again not remaining in place. This migration of the ointment creates lifting of the dressing and exposes the site to additional contamination. In addition, the antibiotic based ointments are ineffective on resistant bacteria and fungi. In fact in a study by S. H. Zinner et al (supra), 30% of the organisms isolated from catheter tips were resistant to the antibiotic ointment.
Other known medical sealants include one disclosed in U.S. Pat. No. 4,621,029 and comprised of a polysiloxane gel. The sealant is water-repellant and, thus, poorly moisture vapor transmissive. Accordingly moisture from the body can collect under this sealant, creating a beneficial environment for bacteria. Furthermore, polysiloxane gels are not capable of complexing with iodine, a substance which exhibits broad-spectrum antimicrobial activity when placed in contact with mammalian skin.
U.S. Pat. No. 4,364,929 discloses a lubricating gel comprising a physiologically compatible colloidal gel-forming polymer, water and an iodophor or a substance capable of forming an iodophor with iodine. These gels are described as lubricants, indicating that they would not have adhesive properties and would be greasy, and therefore incompatible with conventional wound dressings.
G. B. Pat. Specification No. 1,511,563 discloses a crosslinked hydrophilic polymer comprised of 30 to 90 percent by weight water soluble mono-olefinic monomers, with or without 1 to 70 percent by weight water-insoluble monomers, and 10 to 70 percent by weight of a terminally diolefinic hydrophobic macromer. An especially preferred water-soluble monomer is N-vinyl pyrrolidone. These polymers are particularly useful in medical applications such as bandages for wound treatment and body implants, where strength of the polymer article and high permeability of water are required simultaneously. However, these polymers are not adhesive and therefore would not be useful as medical sealants.
Another pressure-sensitive adhesive for medical applications is disclosed in U.K. Pat. application 2,115,431. The adhesive described comprises at least one irradiation crosslinked synthetic organic polymer and an adhesive plasticizer. The crosslinked polymer is formed by subjecting a solution or dispersion of at least one uncrosslinked, synthetic organic polymer (including one which has repeating units derived from an N-vinyl lactam monomer) in a solubilizing plasticizer to ionization radiation energies of at least the equivalent of 100,000 electron volts (x-ray, gamma ray and electron beam irradiation). Those skilled in the art will appreciate that while the use of ionizing irradiation to force chemical reactions can be useful for many applications, the use of ionizing irradiation is not always desirable because of the wide variety of reactive species that can be produced making the process very difficult to control and making the effect of additional constituents very difficult to predict.
Another art involving polymeric matrices that are swelled in water is the hydrogel art. These compositions are covalently crosslinked and are used extensively in contact lenses. Many of these hydrogels are based on polyvinylpyrrolidone and have been extensively used in medical applications. Because of the long experience with use of polyvinylpyrrolidone in medical applications its safety is well known making it a desirable candidate for biocompatible adhesives. While most hydrogels are not adhesive, EPO Appln. No. 83305770.6 (publication 0107376, 02/05/84) describes a hydrogel which has some tack and is recommended for use as a wound dressing. The hydrogel is prepared by dissolving between 15% and 25% by weight polyvinylpyrrolidone in water and crosslinking with ionizing irradiation (1 to 5 Mrads, electron beam). Here again the ionizing radiation process is not desirable.
U.S. Pat. No. 4,543,371 discloses a hydrogel formed by the copolymerization of a hydrophilic dihydroxy alkyl acrylate or methacrylate, a substantially water insoluble alkyl acrylate or methacrylate, one or more additional hydrophilic monomers selected from the group of vinylic monomers, acrylates, and methacrylates, and a crosslinking agent. The resultant hydrogel is nontacky and is preferably used for the formation of contact lenses having greater rigidity than the hydrogel contact lenses of the prior art.
U.S. Pat. No. 3,928,255 discloses chemically joined, phase separated self-cured hydrophilic thermoplastic graft copolymers which are useful in the field of biomedics. These copolymers comprise at least one hydrophilic ethylenically unsaturated monomer or mixtures thereof and at least one copolymerizable hydrophobic macromolecular monomer having a copolymerizable end group which is copolymerizable with said hydrophilic monomer. The resultant hydrogels are nontacky and are preferably used as contact lenses or artificial organs.
U.S. Pat. No. 3,294,765 discloses polymeric matrices of N-vinyl lactams crosslinked with 3,3'-ethylidene bis(N-vinyl-2-pyrrolidone). The patent indicates that polymeric matrices with mechanical properties ranging from thickened solutions to intractable gels are obtained depending on the relative amount of crosslinker used. None are reported to be adhesive.
U.S. Pat. No. 3,907,720 discloses that iodine complexes can be prepared of water swellable crosslinked N-vinyl lactam or N-alkyl-N-vinylamide polymers in the form of porous beads or granules. These complexes are suitable as bactericide and water treatment aids in gravity filtration systems or packed columns, such aids having the advantage of rapid throughput.
The polymeric compositions known in the art have not met the need for a pressure-sensitive medical sealant that has high moisture vapor transmission and is capable of complexing with and releasing iodine. A need also exists for a medical sealant that is in a caulkable form and can be used to surround and seal a catheter site.